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This chapter focuses on the pathogenesis of the acute respiratory distress syndrome (ARDS). Chapter 141 discusses clinical features and management of these disorders.

A 1994 consensus conference defined the spectrum of acute lung injury (ALI)/ARDS as follows: (1) ALI, defined as arterial hypoxemia with a PaO2/FiO2 less than 300, and ARDS, defined as a PaO2/FiO2 less than 200, accompanied by (2) bilateral pulmonary infiltrates, and (3) absence of left atrial hypertension.1 A more recent report, based on the so-called Berlin definition, recommends identification of three categories of ARDS, based upon the degree of hypoxemia alone: (1) mild ARDS (200 < PaO2/FiO2 ≤300 mm Hg), (2) moderate ARDS (100 < PaO2/FiO2 ≤200 mm Hg), or (3) severe ARDS (PaO2/FiO2 ≤100 mm Hg).2 For the purposes of this chapter, both ALI and ARDS will be referred to as ARDS.

A recent comprehensive review of ARDS provides extensive references and illustrations relevant to epidemiology, definitions (including pediatric ARDS), pathogenesis based on experimental and clinical studies, management strategies, and long-term complications of ARDS.3


Pulmonary edema occurs when fluid is filtered into the lungs faster than it can be removed. Accumulation of fluid may have major consequences on lung function because efficient gas exchange cannot occur in fluid-filled alveoli. Lung structure relevant to edema formation and the forces governing fluid and protein movement in the lungs have been the subject of classic and more recent reviews.4,5

Vascular Fluid and Protein Exchange

The essential factors that govern fluid exchange in the lungs are expressed in the Starling equation for the microvascular barrier:

Jv = LpS[(Pc – Pi) – σd(πc – πi)]


Jv = the net fluid-filtration rate (volume flow) across the microvascular barrier

Lp = the hydraulic conductivity (permeability) of the microvascular barrier to fluid filtration (a measure of how easy it is for water to cross the barrier)

S = the surface area of the barrier

Pc = the pulmonary capillary (microvascular) hydrostatic pressure

Pi = the interstitial (perimicrovascular) hydrostatic pressure

πc = the capillary (microvascular) plasma colloid osmotic (or oncotic) pressure

πi = the interstitial (perimicrovascular) fluid osmotic pressure

σd = the average osmotic reflection coefficient of the barrier (a measure of the effectiveness of the barrier in hindering the passage of solutes from one side of the barrier to the other)

The Starling equation predicts the development of two different kinds of pulmonary edema. Increased pressure pulmonary edema occurs when the balance of the ...

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